chr2-112647131-G-A

Variant names:

• chr2-112647131-G-A
• rs4849091
• NM_005415.5:c.303G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_005415.5(SLC20A1):​c.303G>A​(p.Leu101Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,613,440 control chromosomes in the GnomAD database, including 233,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (16545 hom., cov: 31)
  • Exomes 𝑓: 0.54 (216710 hom.)
• Consequence: SLC20A1 NM_005415.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.900
• Publications: 29 publications found

Genes affected

SLC20A1 (HGNC:10946): (solute carrier family 20 member 1) The protein encoded by this gene is a sodium-phosphate symporter that absorbs phosphate from interstitial fluid for use in cellular functions such as metabolism, signal transduction, and nucleic acid and lipid synthesis. The encoded protein is also a retroviral receptor, causing human cells to be susceptible to infection by gibbon ape leukemia virus, simian sarcoma-associated virus, feline leukemia virus subgroup B, and 10A1 murine leukemia virus.[provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 2-112647131-G-A is Benign according to our data. Variant chr2-112647131-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058938.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005415.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC20A1	NM_005415.5	MANE Select	c.303G>A	p.Leu101Leu	synonymous	Exon 2 of 11	NP_005406.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC20A1	ENST00000272542.8	TSL:1 MANE Select	c.303G>A	p.Leu101Leu	synonymous	Exon 2 of 11	ENSP00000272542.3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66562 AN: 151908 Hom.: 16541 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.467

GnomAD2 exomes AF: 0.493 AC: 123453 AN: 250338 AF XY: 0.503

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.480

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.213

Gnomad FIN exome AF: 0.569

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.536

GnomAD4 exome AF: 0.537 AC: 785014 AN: 1461414 Hom.: 216710 Cov.: 53 AF XY: 0.538 AC XY: 390905 AN XY: 726958

African (AFR) AF: 0.192 AC: 6410 AN: 33472

American (AMR) AF: 0.481 AC: 21529 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 14114 AN: 26124

East Asian (EAS) AF: 0.199 AC: 7918 AN: 39690

South Asian (SAS) AF: 0.491 AC: 42386 AN: 86252

European-Finnish (FIN) AF: 0.569 AC: 30414 AN: 53414

Middle Eastern (MID) AF: 0.514 AC: 2963 AN: 5768

European-Non Finnish (NFE) AF: 0.565 AC: 628085 AN: 1111594

Other (OTH) AF: 0.517 AC: 31195 AN: 60386

GnomAD4 genome AF: 0.438 AC: 66585 AN: 152026 Hom.: 16545 Cov.: 31 AF XY: 0.438 AC XY: 32546 AN XY: 74306

African (AFR) AF: 0.204 AC: 8454 AN: 41460

American (AMR) AF: 0.467 AC: 7136 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1840 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1078 AN: 5176

South Asian (SAS) AF: 0.484 AC: 2331 AN: 4816

European-Finnish (FIN) AF: 0.565 AC: 5961 AN: 10542

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38159 AN: 67970

Other (OTH) AF: 0.470 AC: 991 AN: 2110

Alfa AF: 0.512 Hom.: 66179

Bravo AF: 0.425

Asia WGS AF: 0.362 AC: 1259 AN: 3478

EpiCase AF: 0.564

EpiControl AF: 0.568

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC20A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.6
DANN	Benign	0.86
PhyloP100		0.90
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4849091; hg19: chr2-113404708; COSMIC: COSV55611431; COSMIC: COSV55611431;